NIH Dry Spell Parches Researchers

Alex Philippidis

For a year, supporters of increased federal research funding have been decrying the effect of across-the-board budget cuts or sequestration on NIH, warning that the nation’s basic research effort was imperiled by spending reductions that postpone the development of new therapeutics, or at least better understanding of how diseases work.

President Barack Obama didn’t do much to quiet the complaints on March 4 when he unveiled a $3.901 trillion budget for the 2015 federal fiscal year. The proposed budget would give NIH just $30.2 billion in overall program level funding, up just $200 million or less than 1% above FY 2014.

“This level of increase really diminishes our ability to accelerate the pace of medical innovation, which we’re capable of doing right now, but we’re being asked to do it with one hand tied behind our back,” Mary Woolley, president and CEO of the research funding advocacy group Research!America, told GEN.

“There are very few researchers who personally or through their institutions can afford to keep their research going in this dry spell indefinitely,” Woolley said. “The research community is very upset, especially the young scientists. Those are historically the risk takers. They’re the ones engaged in disruptive thinking that’s going to lead to breakthroughs and innovation. It is those very young scientists who are most at risk right now.”

Obama’s spending plan is likely a starting point for what should be a larger increase, since lawmakers in both parties have voiced support for increased NIH funding since the end of the 16-day partial government shutdown in October. But that increase is unlikely to be dramatically higher than the president’s budget if recent history is a guide, since Congress and Obama are already struggling to contain spending.

As a result, the nation’s research labs are unlikely to restore the work, and in some cases the jobs, they were forced to delay or terminate a year ago.

“You Have to Make Choices”

Robert Clarke, Ph.D., D.Sc., co-director of the Breast Cancer Program at the Lombardi Comprehensive Cancer Center in Washington, DC, told GEN he has been unable to rehire the two postdoctoral researchers he laid off after losing $800,000 from a five-year, $7.5 million grant awarded in 2010 by NIH’s National Cancer Institute.

During the grant’s first three years, researchers developed a roadmap or mathematical model for estrogen signaling in breast cancer cells—and by extension, why some cancer cells are susceptible to endocrine therapy while others are not. Researchers also uncovered a single molecule that plays a key role in determining resistance to anti-estrogen therapy used to treat or prevent breast cancer in tens of thousands of women at high-risk for the disease.

The funding cut effectively froze research on the molecule and forced Dr. Clarke and colleagues to narrow the focus of their research program, using criteria that included cost and length of time.

“We need to have more evidence that we’re on the right track. We need to have more preliminary data, and sometimes a few extra papers that are peer-reviewed that help support the strength of the hypotheses that you’re trying to test,” said Dr. Clarke, who is also dean for research at Georgetown University Medical Center.

“We had a number of promising new lines of investigation that we just had to put on the back burner until we can find the resources to pursue them,” he added. “They’re different ways of looking at the question of why some breast cancers respond to hormone-based treatments, and why some don’t, and why some that initially respond at some point become resistant, and the disease recurs.”

Dr. Clarke also expressed concern about the future of research in the U.S. when the overall success rate for winning NIH grants is so low.

During FY 2013, according to NIH, the overall success rate for competing research project grants (RPGs) dipped to 16.8% from 17.6% a year earlier. The average RPG size slid nearly 3%, to $441,404 from $454,588 in FY ’12. Adjusted for inflation, average RPG sizes have fallen 4.5% since 1999, to $277,653.

“That doesn’t sound like the right kind of commitment from our federal government,” Woolley added.

Perhaps most discouraging: The total number of research grant applications received by NIH decreased during FY 2013, to 61,013 from 63,524 the previous year.

TB or Not TB

NIH is among federal agencies that cut research funding following sequestration. The Centers for Disease Control and Prevention (CDC) cut funding 13% to the Tuberculosis Trials Consortium (TBTC), shrinking its budget to $9.2 million following a couple of years of smaller reductions from a peak of $10.6 million. The research group responded by shutting down two of its 20 clinical research sites—one at Duke University, the other in Rio de Janeiro.

Each site has an investigator who relies on TBTC to support between 10% and 20% of salary, as well as one or two study coordinators, 100% of whose salaries are supported by the consortium. When a site closes, they all lose their jobs. The Rio closing was especially troubling since overseas sites are especially counted on to draw heavy patient enrollment in trials, Neil Schluger, M.D., chairman of TBTC’s steering committee, told GEN.

“We do Phase II and Phase III trials. Our trials typically need several hundred patients to enroll. And we’d like to do that as quickly as possible to move our agenda along and answer important questions scientifically, and this just slows down our progress tremendously,” added Dr. Schluger, who is also chief, division of pulmonary, allergy, and critical care medicine at Columbia University Medical Center, where he is also professor of medicine, epidemiology, and environmental health sciences.

TBTC brings together researchers from CDC, domestic and international public health departments, academic medical centers, and selected U.S. Department of Veterans Affairs medical centers, to carry out research concerning the diagnosis, clinical management, and prevention of TB infection and disease.

Delayed by the cuts was a Phase IIb trial looking at high doses of Sanofi’s antibiotic Priftin (rifapentine) in the induction phase of chemotherapy for TB. Based on results of that trial, TBTC plans a Phase III trial assessing a shorter TB treatment regimen of three or four months from the current six months.

The consortium is also still enrolling patients for a study of a new 12-dose regimen for latent TB that could replace the standard 270-dose regimen. “We’re trying to look at the best way to deliver that regimen: Does it have to be by directly through therapy, or can it be delivered by self-administered therapy. That’s a 1,000-person trial that should finish enrolling in another month or so. But all of these things go more slowly when you don’t have enough sites,” Dr. Schluger said.

Younger researchers, he added, see their mentors and other established investigators struggling to get grants renewed and things like that, and wonder how much lower NIH and CDC funding will sink: “They say, ‘Why should I do this? How can anybody live this way? What’s the future in that?’ We really are in the process of losing a generation of people who otherwise might have pursued careers in research.”

And if that happens, the U.S. will lose more than simply leadership in research, but the brainpower needed to tackle the field’s most challenging questions, and as a result, lives that otherwise could have been saved.